The Cell Signaling and Gene Regulation Program (Program 1) brings together a group of basic and translational investigators dedicated to the study of cancer through research in cell signaling, molecular biology, systems biology, developmental biology, and chemistry/drug discovery. The program has 46 members from 13 Departments, and members have a total of $16,459,487 in peer-reviewed funding with $5,012,818 from the NCI. Program members have been highly-productive, with 599 peer-reviewed publications, including 7% that were intraprogrammatic, and 15% interprogrammatic publications. The scientific goals of the Cell Signaling and Gene Regulation Program are to determine the basic cell signaling and gene expression mechanisms that underlie malignancy. To this end, our membership's research focuses on determining the mechanisms whereby genes, and the proteins they encode, function in both normal and cancerous conditions. In the previous funding period, Program 1 has increased its membership size from 25 to 46 members, reflecting a major recruitment of physician-scientists studying basic mechanisms of disease, as well as systems biologists. In addition, the UCCRC's outreach to physical scientists interested in collaborative interdisciplinary cancer research has also enriched the membership of Program 1. Overall, the research objectives of our scientists can be divided into the following five themes: (1) to elucidate the molecular mechanisms of tissue-specific and cell type-specific gene expression; (2) to elucidate the cellular mechanisms underlying cell growth/division and cell survival/death; (3) to understand the multi-faceted mechanisms leading to cancer metastases; (4) to use large-scale, high-throughput systems biology approaches and genetic evolutionary approaches to understand cancer biology; and (5) to discover novel developmental pathways relevant to cancer cell signaling. Although our members' interests are varied, many common themes have emerged. Moreover, in the current funding period, our membership has developed numerous collaborations with clinician scientists both within Program 1 and interprogramatically, reflecting the increasingly cross-disciplinary and translational nature of our research program. Through pilot funding, quarterly membership meetings, a seminar series, an annual retreat, and a strong basic science training program in cancer biology, Program 1 is poised to continue its successful in-depth and basic research focus on cancer biology, while nurturing collaborative science that will enhance clinical care of patients at risk or with cancer.